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Pharmaceutical composition for treatment and prevention of cancers

Active Publication Date: 2011-10-20
TORAY IND INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0027]Antibodies against CAPRIN-1 used in the present invention damage (or impair) cancer cells. Therefore, such antibodies against CAPRIN-1 are useful for treatment or prevention of cancers.

Problems solved by technology

Cancer is the leading cause of death.
In spite of development of new surgical methods and discovery of new anti-cancer agents in recent years, treatment results of cancers are not greatly improved at present except for some cancers.
As a result of antibody administration, not only cancer cells, but also normal cells, on which a target antigen has been expressed can be damaged, thereby causing a side (or adverse) effect, which becomes problematic.

Method used

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  • Pharmaceutical composition for treatment and prevention of cancers
  • Pharmaceutical composition for treatment and prevention of cancers
  • Pharmaceutical composition for treatment and prevention of cancers

Examples

Experimental program
Comparison scheme
Effect test

example 1

Identification of New Cancer Antigen Protein by SEREX Method

[0155](1) Construction of cDNA Library

[0156]Total RNA was extracted from a testis tissue of a healthy dog by an Acid guanidium-Phenol-Chloroform method and then a polyA RNA was purified according to protocols included with an Oligotex-dT30 mRNA purification Kit (Takara Shuzo Co., Ltd.).

[0157]A canine testis cDNA phage library was synthesized using the thus obtained mRNA (5 μg). The cDNA phage library was constructed using a cDNA Synthesis Kit, a ZAP-cDNA Synthesis Kit, and a ZAP-cDNA GigapackIII Gold Cloning Kit (STRATAGENE) according to protocols included with the kits. The size of the thus constructed cDNA phage library was 7.73×105 pfu / ml.

(2) Screening of cDNA Library using Serum

[0158]Immunoscreening was performed using the above constructed canine testis cDNA phage library. Specifically, host Escherichia coli (XL1-Blue MRF’) was infected with the phage on an NZY agarose plate (Φ90×15 mm) so as to obtain 2210 clones. E. ...

example 2

Antitumor Effects (ADCC Activity) of Antibody against CAPRIN-1 upon Cancer Cells

[0172]Next, it was examined whether or not an antibody against CAPRIN-1 would be able to damage CAPRIN-1-expressing tumor cells. Evaluation was carried out using the polyclonal antibody against a human CAPRIN-1-derived peptide prepared in Example 1. Two types of human breast cancer cell lines (T47D and MDA-MB-157) (106 cells each), in which CAPRIN-1 expression had been confirmed, were separately collected into a 50-ml centrifugal tube. Chromium 51 (100 μCi) was added thereto, followed by incubation at 37° C. for 2 hours. Thereafter, cells were washed 3 times with an RPMI1640 medium containing 10% fetal calf serum and added to wells (103 cells per well) in 96-well V-bottom plates. The above polyclonal antibody against a human CAPRIN-1-derived peptide was added thereto (1 μm per well). Further, lymphocytes separated from rabbit peripheral blood were added thereto (2×105 cells per well), followed by culture...

example 3

Preparation of New Human Cancer Antigen Proteins

(1) Preparation of Recombinant Protein

[0174]A recombinant protein of a human homolog gene was prepared by the following method based on the gene of SEQ ID NO: 1 obtained in Example 1. PCR was performed by repeating 30 times a cycle of 98° C. / 10 seconds and 68° C. / 2.5 minutes using a Thermal Cycler (BIO RAD) and a reaction solution adjusted to a total amount of 50 μl through addition of each reagent and an attached buffer (1 μl of cDNA (which was from a variety of tissue / cell-derived cDNAs prepared in Example 1 and observed for their expression by RT-PCR), 2 types of primers (0.4 μM each; SEQ ID NOS: 38 and 39) containing Sad and XhoT restriction enzyme cleavage sequences, 0.2 mM dNTP, 1.25 U PrimeSTAR HS polymerase (Takara Shuzo)). The above 2 types of primers were used to amplify the region encoding the full-length amino acid sequence of SEQ ID NO: 2. After PCR, the thus amplified DNA was subjected to 1% agarose gel electrophoresis an...

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Abstract

The present invention relates to a pharmaceutical composition for treatment and / or prevention of cancer, which comprises, as an active ingredient, an antibody or fragment thereof having an immunological reactivity with a CAPRIN-1 protein or a fragment thereof comprising 7 or more consecutive amino acids.

Description

TECHNICAL FIELD[0001]The present invention relates to a novel medical use of antibodies to CAPRIN-1 or fragments thereof as, for example, therapeutic and / or preventive agents for cancer.BACKGROUND OF INVENTION[0002]Cancer is the leading cause of death. Treatment currently performed for cancer is mainly surgical therapy, which can be combined with radiation therapy or chemotherapy. In spite of development of new surgical methods and discovery of new anti-cancer agents in recent years, treatment results of cancers are not greatly improved at present except for some cancers. Through a recent progress of molecular biology and cancer immunology, antibodies that are specifically reactive with cancers, cancer antigens recognized by cytotoxic T cells, as well as the genes encoding the cancer antigens, have been identified, and expectations for specific immunotherapies targeting cancer antigens have been raised (Tsuyoshi AKIYOSHI, “Gan To Kagaku-Ryoho (Cancer and Chemotherapy),” 1997, vol. 2...

Claims

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Application Information

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IPC IPC(8): A61K39/395A61P35/00A61P35/02C07K16/18
CPCC07K16/3015C07K16/3053C07K2317/734C07K2317/565C07K2317/732C07K2317/24A61K2039/505C07K16/30C07K2317/56A61P1/04A61P11/00A61P15/00A61P25/00A61P35/00A61P35/02A61K39/39558C07K2317/34
Inventor OKANO, FUMIYOSHIIDO, TAKAYOSHISAITO, TAKANORIKOBAYASHI, SHINICHI
Owner TORAY IND INC
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